Near Infrared Diffused Light Imaging with Ultrasound Guidance: We propose to explore the utility of a novel hybrid imaging technique for: 1) Accurate diagnosis of breast lesions and therefore reduction of benign biopsies;and 2) Assessing chemotherapy response and evaluating treatment efficacy. The hybrid technique is implemented by simultaneously deploying near infrared (NIR) optical sensors and a commercial ultrasound transducer mounted on a hand-held probe, and utilizing coregistered lesion structure information provided by ultrasound to improve the inverse optical tomography reconstruction. As a result, the optical tomography has overcome problems associated with the intense light scattering and has provided reliable tumor angiogenesis distributions. Preliminary results with a group of biopsied patients have shown that early-stage invasive cancers may be distinguished by an average of twofold greater total hemoglobin concentration when compared to fibroadenomas and other benign lesions. Early results obtained from advanced cancers have shown that the angiogenesis distribution is highly distorted and heterogeneous, and the distorted distributions correlate with histological microvessel counts and can be used to assess chemotherapy response. In this renewal application, we propose larger-scale clinical studies to further validate these initial results. The proposed specific aims in this application are: 1) To estimate and correct chest-wall induced NIR diffusive wave distortion, which often occurs in patients with a smaller volume of breast tissue, and to implement on-line optical imaging reconstruction by incorporating a digital signal processing module;2) To upgrade prototype NIR systems to imaging platforms;3) To validate the initial sensitivity, specificity, positive predictive value and negative predictive value obtained from optical tomography/ultrasound in distinguishing benign and early-stage malignant breast tumors from a larger patient pool. Approximately 300 patients who will undergo ultrasound-guided biopsy will be recruited to this study from the University of Connecticut Health Center and Hartford Hospital;To perform a pilot study in diagnostic setting at both institutions;and 4) To validate the optical tomography/ultrasound as a valuable imaging tool in assessing chemotherapy response and evaluating treatment efficacy. Approximately 40 patients who will undergo chemotherapy treatments will be recruited to this pilot study from both institutions.